Ranitidine is a best-selling drug used to reduce high stomach acid. Therefore, it is widely used in the treatment of conditions such as gastroesophageal reflux, ulcers in the stomach and bowel, erosive esophagitis, and Zollinger-Ellison syndrome. Read on to learn more about this medication, its health benefits, and main adverse effects.

Disclaimer: By writing this post, we are not recommending this drug. Some of our readers who were already taking the drug requested that we commission a post on it, and we are simply providing information that is available in the scientific literature. Please discuss your medications with your doctor.

What is Ranitidine (Zantac)?

Ranitidine is a drug that decreases stomach acid production and is therefore used in the treatment and prevention of disorders related to excessive stomach acid [1].

Developed in 1977, it was first introduced into the market in 1981 and quickly became the best-selling drug worldwide [2].

The main brand names for ranitidine are Zantac® and Taladine®.

Ranitidine is a histamine blocker. It binds to H2-receptors in the stomachs acid-producing cells and prevents their activation by histamine [3].

Prescription ranitidine comes as tablets (oral and effervescent), capsules, and syrup. This medication is mainly used to treat [1]:

  • Ulcers of the stomach and bowel
  • Esophagus inflammation
  • Gastroesophageal reflux disease (GERD)
  • Zollinger-Ellison syndrome

It is also sold over-the-counter (OTC) as 75 mg and 150 mg tablets to prevent symptoms of excessive acid in the stomach such as [4, 5]:

  • Heartburn
  • Acid indigestion

The most commonly reported adverse effects of ranitidine during prescription and OTC treatments include [6]:

Ranitidine Mechanism of Action

Histamine is a compound that is produced by white blood cells (mast cells and basophils), platelets, immune cells (lymphocytes), brain cells, and secreting cells in stomach glands (enterochromaffin cells) [7].

In the stomach, histamine is produced by enterochromaffin cells and activates the cells that produce acid (parietal cells) by binding to the H2-receptors on their surface [8].

Ranitidine and other H2-receptor blockers were designed by using histamine as a starting point and modifying its chemical structure [9].

These chemicals compete with histamine for binding to the H2-receptor. The reversible interaction between a blocker and the receptor prevents the binding of histamine, and thus the activation of acid production [10].

Uses of Ranitidine

1) Gastroesophageal Reflux Disease (GERD)

Gastroesophageal reflux disease (GERD) is the abnormal entry of stomach acid into the esophagus. The main symptoms of this disease, which affects 20% of the US adult population at least once a week, are heartburn and regurgitation [11].

GERD normally occurs when the muscle (lower esophageal sphincter) closing the stomach opening cannot counteract the internal pressure of this organ [12, 13].

The main factors triggering GERD are [14, 15]:

  • Intake of fatty and spicy food
  • Intake of cola and alcohol
  • Stress
  • Exercise
  • Changes in body position

Ranitidine reduced GERD symptoms such as heartburn and esophagitis in several trials [16, 17].

It outperformed an antacid (calcium carbonate) in relieving heartburn in a trial (double-blind randomized controlled trial) of 155 GERD patients [18].

Low doses of this drug decreased stomach acid for 9 hours in a study (double-blind randomized controlled trial) on 24 healthy individuals [19].

High doses of ranitidine showed better GERD relieving capacity in 2 trials (double-blind randomized controlled trial) on 12 and 26 patients [20, 21].

However, one study (double-blind randomized controlled trial) on 18 GERD patients showed the development of tolerance to the medication after long-term treatment with ranitidine, resulting in a reduced efficiency [22].

In a trial (double-blind randomized controlled trial) on 29 children, low doses of ranitidine reduced stomach acid [4].

According to one study (double-blind randomized controlled trial) on 18 pregnant women, ranitidine twice daily relieved GERD symptoms more efficiently than the same dose once daily [23].

However, PPIs generally outperform ranitidine in the treatment of this disease.

Several studies showed a better efficiency of omeprazole compared to ranitidine in the management of GERD symptoms [24, 25, 26, 27].

In several studies, lansoprazole treated GERD more efficiently than ranitidine [28, 29].

Pantoprazole also relieved GERD symptoms more efficiently than ranitidine [30, 31].

Both ranitidine and omeprazole were equally efficient in treating GERD symptoms in a study (double-blind randomized controlled trial) on 76 children [32].

2) Heartburn

Heartburn is a burning and painful sensation in the chest and upper stomach that is normally due to the entry of stomach acid into the esophagus and is the main symptom of gastroesophageal reflux disease (GERD) [33].

It is generally well controlled with antacids. While H2-receptor blockers and PPIs prevent the formation of acid in the stomach, antacids neutralize it after its production [34].

In a trial (double-blind randomized controlled trial) on 94 patients with self-perceived heartburn taking either an antacid (Maalox) or ranitidine, the antacid was faster in relieving heartburn symptoms [35].

According to a randomized, 4-way crossover evaluation on 26 patients with frequent meal-induced heartburn, ranitidine was faster at reducing stomach acidity, while the effect of the antacid (calcium carbonate) was faster in the esophagus [36].

In a longer-term trial (double-blind randomized controlled trial) of 155 patients suffering from heartburn frequently, it was more effective than antacid (calcium carbonate) in relieving heartburn, curing erosive esophagitis, reducing pain, and improving life quality [18].

In several trials, ranitidine efficiently relieved heartburn symptoms within 30 to 60 minutes and lasted up to 12 hours [37, 38, 15, 39].

Ranitidine reduced heartburn symptoms and esophagus sensitivity to acid in 2 independent trials [40, 41].

However, doubling the dose to 300 mg did not improve the recovery rate in the first trial [40].

3) Erosive Esophagitis

A small proportion of patients with gastroesophageal reflux disease (GERD) develop erosive esophagitis, in which the lining of the esophagus is inflamed and worn away [42].

Patients whose esophagus is in contact with stomach acid for extended periods have the highest risk of developing erosive esophagitis [43].

High doses of ranitidine were effective in treating erosive esophagitis in several studies [44, 45, 46].

In a study (randomized controlled trial) on 7 patients with erosive esophagitis, low doses of ranitidine decreased the exposure of the esophagus to acid but failed to reduce it to normal values [47].

In several trials, omeprazole treated erosive esophagitis more effectively than the combination of ranitidine and metoclopramide [48, 49].

Similarly, rabeprazole and lansoprazole were more effective than this drug against erosive esophagitis in multiple studies [50, 51].

In a trial (double-blind randomized controlled trial) of 386 patients with erosive esophagitis being treated with proton pump inhibitors (PPIs), adding ranitidine improved heartburn symptoms in the short term, but patients eventually developed tolerance [52].

4) Zollinger-Ellison Syndrome

Zollinger-Ellison syndrome is the presence of a tumor, normally in the pancreas, bowel, or nodes on the stomach, which produces a hormone (gastrin) that stimulates the increased release of stomach acids [53].

The symptoms are caused by the excess of acid and include [54]:

  • Ulcers in the bowel
  • Gastroesophageal reflux
  • Diarrhea
  • Nausea
  • Loss of appetite
  • Bleeding

The excessive acid production associated with Zollinger-Ellison syndrome can be treated with H2-receptor blockers. Due to its low side effects and limited interactions with other drugs, ranitidine is often the treatment of choice [55].

High doses of this drug have been successfully used in the management of this syndrome [56, 57, 58, 59].

Low doses of omeprazole have been used as an alternative to H2-receptor blockers [60, 61, 62].

Ranitidine was effectively used in managing Zollinger-Ellison syndrome in pregnant women [63].

5) NSAID-Induced Complications

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed to treat inflammatory conditions and reduce pain. Their long-term use is associated with increased risk of developing ulcers in the stomach and bowel [64, 65].

Ranitidine prevented and healed NSAID-induced ulcers in several clinical trials [66, 67, 68, 69, 70].

In 2 studies in rats, it reduced stomach ulceration and bleeding caused by NSAIDs [71, 72].

Given their stronger action, PPIs have been included in trials comparing their efficiency to that of ranitidine against NSAID-induced ulcers.

In a study (double-blind randomized controlled trial) of 541 patients who required NSAID treatment and had ulcers in the stomach or bowel, omeprazole was more effective than ranitidine in healing and preventing ulcers [73].

In 2 studies, the healing rate of NSAID-induced stomach ulcers was higher in patients taking lansoprazole than in those taking ranitidine [74, 75].

The efficiency of esomeprazole in healing NSAID-induced stomach ulcers was higher in patients taking esomeprazole than in those taking ranitidine in one study (double-blind randomized controlled trial) of 406 patients, but comparable in another one (double-blind randomized controlled trial) of 440 patients [76, 77].

6) Ulcers

Stress-Induced Ulcers

Critically ill patients, such as those in intensive care units, are more prone to stomach ulcers [78].

In some cases, the ulcers can cause severe bleeding and lead to complications (such as anemia, shock, or chest pain) and death [79].

Because stress-induced ulcers are uncommon at low acid levels in the stomach, H2-receptor inhibitors are very popular for the prevention of ulcers [80].

In a study (double-blind randomized controlled trial) of 37 patients in intensive care units, ranitidine efficiently reduced stomach acidity, thus preventing the appearance of stress-induced ulcers [81].

Short-term treatment with ranitidine prevented the appearance of stomach ulcers in a trial (double-blind randomized controlled trial) of 48 newborn babies in the neonatal intensive care unit [82].

However, in a study (double-blind randomized controlled trial) of 97 patients in intensive care units with normal liver and kidney function subjected to long-term mechanical ventilation, ranitidine did not decrease the incidence rate of stress-induced ulcers [83].

In a meta-analysis of 3 studies, omeprazole was as effective as ranitidine in the prevention of stress-induced ulcers [84].

In turn, in 2 trials, sucralfate (a drug that binds to ulcers and creates a protective barrier against stomach acids) was at least as effective as ranitidine in preventing the appearance of stress-induced ulcers and reduced the risk of pneumonia [85, 86].

Stomach and Intestinal Ulcers

Ulcers are breaks in the lining of the stomach or first part of the small intestine.

The main symptoms are [87]:

  • Stomach pain
  • Loss of appetite
  • Regurgitation
  • Nausea
  • Vomiting of blood
  • Weight loss

Ranitidine has been successfully used to treat ulcers in the stomach and bowel in several trials [88, 89, 90, 91].

A single bedtime dose of 300 mg was as safe and effective in healing ulcers as the standard dose of 150 mg twice per day in several studies [92, 93, 94].

In several trials on patients with healed stomach and bowel ulcers, ranitidine was an effective maintenance therapy to prevent relapse [95, 96, 97, 98].

In several studies, omeprazole was more effective than a standard dose of ranitidine in the treatment of stomach and bowel ulcers [99, 100, 101, 102].

Helicobacter Pylori-Induced Ulcers and Complications

Helicobacter pylori (H. pylori) a bacteria that infects the digestive system. Although most infected individuals do not show symptoms of the disease, infection with this bacteria is responsible for most ulcer cases diagnosed [103].

Ranitidine bismuth citrate, previously sold under the brand name Titrec® and now available as a generic drug, is an effective treatment against H. pylori-induced ulcers. This drug combines the acid-decreasing action of ranitidine and the antimicrobial and mucosal-protective roles of bismuth [104].

The combination of ranitidine bismuth citrate with the antibiotic clarithromycin was more effective in healing ulcers and eradicating H. pylori than ranitidine bismuth citrate alone in several studies [105, 106, 107, 108].

A study (double-blind randomized controlled trial) on 229 patients showed that amoxicillin could be used as an alternative to clarithromycin in patients intolerant or resistant to this antibiotic [109].

The healing effect is enhanced by designing a triple therapy combining both amoxicillin and clarithromycin, as seen in two double-blind randomized controlled trials (on 102 and 137 patients) [110, 111].

In a study (double-blind randomized controlled trial) on 520 patients with duodenal ulcer and H. pylori infection, dual therapy with clarithromycin and omeprazole was as effective as one with this antibiotic and ranitidine bismuth citrate [112].

Both ranitidine bismuth citrate and omeprazole were equally effective in triple therapies with amoxicillin and clarithromycin in several studies [113, 114, 112, 115].

However, ranitidine bismuth citrate in triple therapy with amoxicillin and clarithromycin eradicated H. pylori more efficiently than all PPIs except rabeprazole in a study (double-blind randomized controlled trial) on 379 patients [116].

7) Prevention of Acid Aspiration During Surgery

Acid aspiration is the inhalation of regurgitated stomach acids into the lungs. This complication may occur during surgical procedures [117] and is particularly harmful to patients when the stomach is full and the acid level is high [118].

In a study (double-blind randomized controlled trial) on 271 patients about to undergo surgery, ranitidine twice per day reduced both stomach content volume and acid levels [119].

Intake of water plus ranitidine prior to surgery reduced their risk of acid aspiration and improved their behavior in a trial (double-blind randomized controlled trial) on 75 children [120].

In a study (double-blind randomized controlled trial) on 120 children, the combination of ranitidine with pirenzepine reduced both stomach content volume and acidity [121].

PPIs like omeprazole and pantoprazole were as effective as ranitidine against acid aspiration in several trials, [122, 123, 124].

8) Inhibition of Allergic Response

Because they prevent histamine activity, H2-receptor blockers like ranitidine may reduce the allergic response to some agents [125].

Ranitidine relieved the symptoms of skin allergic reactions in several trials [126, 127, 128, 129].

In 2 clinical trials of patients with skin allergic conditions, it enhanced the healing effects of the therapy with H1-receptor blockers [130, 131].

Ranitidine was effective against some symptoms of allergic nose inflammation in 2 studies, [132, 133].

Henoch-Schönlein vasculitis is the inflammation of blood vessels caused by the allergic reaction to infections or drugs.

Its main symptoms include [134]:

  • Red- or purple-colored spots on the skin
  • Arthritis
  • Stomach pain
  • Stomach and bowel bleeding
  • Blood in the urine

In a trial (double-blind randomized controlled trial) on 12 patients with Henoch-Schönlein vasculitis, treatment with ranitidine reduced the duration and severity of stomach pain and bleeding [135].

9) Gut Bleeding

Gut bleeding is a condition in which blood vessels of the stomach, esophagus, or bowel are broken. It can be life-threatening if it affects large vessels [136].

Its most common causes are:

  • Ulcers in the stomach and bowel [137]
  • Mallory-Weiss tear [138]
  • Stress-induced stomach inflammation [139]
  • Dieulafoy lesions [140]
  • Dilated veins in the stomach [141]

Ranitidine effectively controlled acute gut bleeding in several trials [142, 143, 144].

In 2 trials, it reduced gut bleeding by reducing the acid level of the stomach [145, 146].

Omeprazole was more effective than ranitidine in treating upper gut bleeding in a study (double-blind randomized controlled trial) on 92 patients [147].

In a multi-center trial (double-blind randomized controlled trial) on 1200 patients requiring mechanical ventilation, ranitidine reduced gut bleeding more efficiently than sucralfate [148].

However, the evidence for the effects of ranitidine and sucralfate in preventing gut bleeding in critically ill patients was found insufficient in multiple studies (double-blind randomized controlled trial, meta-analyses) [149, 150, 151].

10) Bowel Inflammation

Inflammatory bowel disease is the long-term inflammation of the intestines, suspected to be due to a malfunction of the immune system.

Two main types of inflammatory bowel disease are [152]:

The main symptoms common to both types of inflammatory bowel disease are:

  • Diarrhea
  • Fever
  • Fatigue
  • Stomach pain and cramps
  • Blood in the feces
  • Reduced appetite
  • Weight loss

Increased production of both histamine and its by-products are observed in patients with inflammatory bowel disease [153, 154, 155, 156].

By preventing the action of histamine, H2-receptor blocking like ranitidine may improve the symptoms of bowel inflammation.

11) Colorectal Cancer Therapy

H2-receptor blockers prevent 3 cancer-promoting effects of histamine:

  • Increased activity of immune-suppressing cells [157]
  • Prevention of tumor recognition by immune cells [158]
  • Promotion of cancer cell growth [159]

In a trial (double-blind randomized controlled trial) on 560 patients with cancer in the large bowel who underwent tumor removal, treatment with ranitidine for 5 years improved survival in those who did not receive blood transfusions during the surgical procedure [160].

The combination of ranitidine with low doses of the cytokine IL-2 increased the activity of natural killer cells in blood from 25 patients with cancer in the large bowel [161].

In cell trials, ranitidine reduced growth and increased death of colorectal cancer cells [162].

Side Effects of Ranitidine

Ranitidine is frequently used worldwide and generally well tolerated.

A review of 21 trials concluded that ranitidine doses of 150 to 600 mg/day are equally safe in elderly and non-elderly patients [163].

The frequency of the main adverse effects of ranitidine in elderly and non-elderly patients [163].

Adverse effects can, however, occur in up to 5% of patients. Those most frequently reported are [1]:

1) Stomach and Bowel

The most frequent events in this system are [6]:

  • Nausea and/or vomiting (2.6-6.8%)
  • Diarrhea (1.4-4.1%)
  • Stomach pain (1.3-1.8%)

These effects tend to improve with continuous treatment. Other less frequent (up to 2%) side effects include:

  • Constipation
  • Heartburn
  • Dry mouth
  • Gas
  • Pancreas inflammation

Stomach and bowel cancer occurred at a rate of 0.2 per million patients treated, but cannot be associated with ranitidine intake [164].

2) Brain

Most common effects of ranitidine on the brain are [6]:

  • Confusion (2.1 events per million)
  • A Headache (2.1 events per million)
  • Dizziness (1.7 events per million)

The proportion of affected patients increases with age and among hospitalized patients, as well as in those with liver or kidney failure. The symptoms are quickly reversed by stopping the treatment [165].

Less frequently reported reactions include:

  • Sleepiness
  • Sleeplessness
  • Disorientation
  • Hallucinations
  • Agitation
  • Delirium

3) Skin

Skin reactions associated with ranitidine intake include [6]:

  • Rash (2.9 events per million)
  • Itching (1.9 events per million)
  • Hives (1.7 events per million)
  • Baldness (1.3 events per million)

The following reactions have been observed less frequently:

  • Toxic skin necrolysis (0.08 events per million) [166]
  • Stevens-Johnson syndrome (0.07 events per million) [167]

4) Liver

Liver injuries caused by the use of ranitidine are rare [168].

The most common liver abnormalities associated with ranitidine are [6]:

  • Increased levels of liver enzymes (5.9 events per million)
  • Hepatitis (1.1 events per million)

5) Hormone Production

Ranitidine does not alter the function of the thyroid, hypothalamus, pituitary, or sex glands [169, 170].

Breast growth has been reported in 0.2 to 1.3 male patients per million [1].

A small rise in prolactin release during ranitidine treatment was observed in 2 studies [171, 172].

6) Heart

The most common effects (0.2 to 0.3 events per million) on the heart include [6]:

  • Low heart rate
  • Heart block
  • High heart rate
  • Irregular heart rate
  • Hypertension

However, no differences were found between the ranitidine and placebo treatment groups [173].

7) Blood Composition

No evidence of change in hemoglobin concentration and red blood counts has been found with ranitidine [6].

In very rare cases, patients taking ranitidine had lower counts of white blood cells and platelets. However, the incidence was lower than that found in the general population [174].

8) Kidneys

Although ranitidine is mostly eliminated through the urine, no evidence of kidney damage associated with this drug has been found. Dose reduction is only recommended in patients with strong kidney failure [6].

9) Other

Because it reduces stomach acid, ranitidine may impair iron absorption [175, 176].

On very rare occasions, patients taking ranitidine have developed a gout-like joint inflammation [177].

One patient with eye nerve damage suffered from increased eye pressure after taking cimetidine and ranitidine [178].

One patient suffered from airway narrowing, breath shortness, and cough after intake of ranitidine [179].

A case of a male patient suffering from impotence during treatment with ranitidine was reported [180].

Anaphylaxis (a fast, life-threatening allergic reaction) can occur in 0.86 patients per million [181].

Injection of ranitidine has caused 3 cases of heart arrest [182, 183, 184].

Drug Interactions of Ranitidine

Due to its acid-blocking activity, ranitidine reduces the absorption of drugs requiring acid in the stomach, such as:

  • HIV medication (Atazanavir, Delavirdine, and Fosamprenavir) [185, 186, 187]
  • Antifungal drugs (Itraconazole and Ketoconazole) [188, 189]
  • Cancer medication (Gefitinib, Dasatinib, and Erlotinib ) [190, 191, 192]
  • Antibiotics (Enoxacin, Cefpodoxime, Bacampicillin, and Cefuroxime) [193, 194, 195, 195]

In turn, it increases the absorption of drugs requiring low acid, such as the sedatives:

  • Triazolam [196]
  • Midazolam [197]

In a study (double-blind randomized controlled trial) on 12 healthy volunteers, the intake of ranitidine increased absorption of the HIV medication saquinavir. However, the effect was independent of ranitidine’s activity against acid production [198].

Absorption of ranitidine and other H2-receptor blockers is reduced by:

  • Antacids [199]
  • Cisapride (enhancer of stomach and bowel movements) [200]
  • Sucralfate (ulcer medication) [201]

Ranitidine binds to the cytochrome P450, thus slowing down the elimination of the following drugs through the kidneys and liver [10]:

  • Procainamide (treatment of irregular heart rates) [202]
  • Triamterene (treatment of hypertension and fluid retention) [203]
  • Midazolam (sedative) [204]

It is thus important to adjust the doses of these medications when used in combination with ranitidine.

The fact that ranitidine also decreases nicotine elimination can be especially relevant to smokers trying to give up or reduce this habit [205].

Ranitidine reduced breakdown of warfarin (blood thinner medication) in a trial (double-blind randomized controlled trial) of 10 patients, but 6 other studies failed to reproduce this result [206, 6].

It increased blood alcohol levels by accelerating stomach emptying in conditions mimicking social drinking [207, 208].

In a study (double-blind randomized controlled trial) on 12 diabetic patients, ranitidine enhanced the effect of glipizide (drug lowering blood sugar levels) [209].

In turn, it increased both blood sugar and insulin levels when combined with glibenclamide (a drug that lowers blood sugar levels) in a study (double-blind randomized controlled trial) on 15 healthy volunteers [210].

Contraindications of Ranitidine

Safety and efficiency of this drug have not been sufficiently described in patients younger than 1 month [211].

In a trial (double-blind randomized controlled trial) on 29 children aged 4 to 11 years old with stomach acidity, treatment with 75 mg/day was both effective and safe [4].

The incidence of the most common side effects on the nervous system (confusion, headaches, and dizziness) increased in elderly and chronically ill patients, as well as in those with kidney failure [212, 165].

Ranitidine may increase the risk of developing pneumonia in critically ill patients [213].

In rare occasions, ranitidine has been reported to cause:

  • Porphyria [214]
  • Stomach cancer [215]

It should be avoided in patients suffering from these conditions.

Because ranitidine is mostly eliminated through urine and partly broken down in the liver, patients with severe kidney and liver diseases should avoid or moderate its intake [216].

Ranitidine is significantly removed by hemodialysis and therefore should be taken after this procedure [217].

Finally, it must be avoided by patients with an allergy to H2-receptor blockers [218].

Ranitidine Use During Pregnancy and Breastfeeding

A study of pregnancy databases, including 1148 cases of women exposed to H2-receptor blockers, concluded that these drugs are safe, given their lack of association with [219]:

  • Infant risk of dying
  • Premature delivery
  • Low birth weight
  • Poor infant wellness (low APGAR scores)

Ranitidine is transported into breast milk. Because the peak concentration occurs 12 hours after its intake, breastfeeding is recommended 1 to 2 hours after drug use to reduce exposure to the baby [220].

Forms and Dosage of Ranitidine

Oral ranitidine is mostly sold in the following forms [221, 222]:

  • Tablets: 75, 150, and 300 mg
  • Capsules: 150 and 300 mg
  • Syrup: 75 mg/5 ml

For patients who cannot take ranitidine by mouth, flasks of ranitidine-HCl (25 mg/ml) are available for injection [223].

The most common over-the-counter doses to treat and prevent heartburn and acid indigestion are 75 and 150 mg per use per day [5].

Doubling the standard dose to 300 mg of ranitidine twice per day does not improve its efficiency in treating gastroesophageal reflux symptoms [40].

In patients suffering from stomach and bowel ulcers, one single dose of 300 mg ranitidine daily is as effective as two doses of 150 mg per day [224].

In the treatment of erosive esophagitis, the recommended doses are 300 mg twice daily or 150 mg per day 4 times daily [46].

Zollinger-Ellison syndrome can be treated with very high doses (up to 2.1 g ranitidine per day) [225].

Ranitidine is very safe and doses up to 6 g per day are generally well tolerated [226].

The incidence of overdose cases has been highest among children under 6 months and patients with kidney failure. The main symptoms of overdose include [227, 228]:

  • Sleepiness
  • Confusion
  • Disorientation
  • Nausea
  • Dizziness

Limitations and Caveats

Studies on the role of ranitidine in healing and preventing stress-induced ulcers show contradicting results [81, 83].

The evidence for the effects of ranitidine on skin allergic reactions is based on a few studies of a relatively small size with a certain risk of bias [229].

Evidence for the effects of ranitidine and sucralfate in preventing gut bleeding in critically ill patients was found insufficient in several studies [149, 150, 151].

The healing effect of ranitidine on intestinal bleeding is mostly speculated based on the role of histamine and its by-products in these diseases [153, 154, 155, 156].

More evidence is needed to evaluate the efficiency of ranitidine in colorectal cancer therapy [160].

PPIs vs. H2-Receptor Blockers

Stomach acid is produced by the presence of protons (H+).

The hydrogen potassium (H+/K+) ATPase is the enzyme that accumulates acid in the stomach by exchanging potassium from the stomach with protons from the parietal cells [230].

This enzyme is found inside parietal cells in the inner lining of the stomach. Upon binding of histamine to the H2-receptors on these cells, the H+/K+ ATPase moves to the cell surface and turns into its activated shape [231].

As opposed to H2-receptor blockers, which inactivate one of the signals that trigger acid production, proton pump inhibitors (PPIs) block the main enzyme of the process: H+/K+ ATPase [232, 233].

Because they target the last step of acid production and block the enzyme, the effect of PPIs is stronger and lasts longer than that of H2-receptor blockers [234].

PPIs are sold as inactive, neutrally charged drugs that cross membranes and accumulate in parietal cells. The high acidity in these cells then transforms PPIs into their active form, which binds to the H+/K+ ATPase and blocks it [235].

The main commercial drugs belonging to this category are [231]:

  • Omeprazole (Losec®)
  • Lansoprazole (Prevacid®)
  • Pantoprazole (Protonix®)
  • Rabeprazole (Aciphex®)
  • Esomeprazole (Nexium®)
  • Dexlansoprazole (Dexilant®)

While H2-receptor blockers have a rapid action of short (less than 12 hours) duration, PPIs have a stronger and more durable (up to 3 days) action that also takes longer to start working [236, 237].

H2-receptor blockers are thus preferred to treat mild, occasional symptoms (episodic heartburn and acid indigestion, or acid aspiration during surgery), while PPIs are used with stronger, chronic disorders (chronic gastroesophageal reflux disease, erosive esophagitis, and ulcers) [238, 239, 240].

Because of their stronger action, PPIs showed increased efficiency over H2-receptor blockers in clinical trials on patients with:

  • Gastroesophageal reflux disease [241]
  • Acid indigestion [242]
  • Erosive esophagitis [51]
  • Stress-induced ulcer [243]

Although both H2-receptor blockers and PPIs are usually well tolerated, it is important to take their differential adverse effects into consideration. Some risks associated with long-term treatment with PPIs include:

  • Magnesium deficiency [244]
  • Increased risk of hip fracture [245]
  • Bacterial infections in the digestive system [246, 247, 248]
  • Pneumonia [249]
  • Chronic kidney disease [250]
  • Dementia [251]

Ranitidine vs. Other H2-Receptor Blockers

Besides ranitidine, the commercial H2-receptor blockers most widely employed are [252]:

  • Cimetidine (Tagamet®)
  • Famotidine (Pepcid®)
  • Nizatidine (Axid®)

Ranitidine vs. Cimetidine

Cimetidine is available in 200, 300, 400, and 800 mg tablets, as a syrup (200 mg/5 ml), as a 100 or 200 mg/5 ml suspension, as intravenous injection (100 mg/ml), and an intravenous infusion (4 mg/ml). Cimetidine is 4 to 5 times less powerful than ranitidine [10].

As opposed to ranitidine, which is also broken down in the liver, cimetidine is almost exclusively eliminated in the urine [253, 254].

Because it binds to the male sex hormone (testosterone) receptors, long-term use of cimetidine can cause loss of libido, impotence, and breast growth in men [10].

In a trial (double-blind randomized controlled trial) on 1,336 patients with gastroesophageal reflux, a 200 mg dose of cimetidine was as efficient as 75 mg of ranitidine in reducing heartburn symptoms [255].

Treatments with ranitidine (1 to 2 mg/kg per dose) and cimetidine (10 mg/kg per dose) were equally effective in relieving the symptoms in a study (double-blind randomized controlled trial) on 169 children with acid indigestion [256].

Additionally, 7.8 g cimetidine/day reduced the symptoms as efficiently as 2.1 g ranitidine/day in a trial (double-blind randomized controlled trial) on 9 patients with Zollinger-Ellison syndrome [257].

Cimetidine (200 mg 3 times per day) was as effective as ranitidine (150 mg twice per day) in healing stomach ulcers in one study (double-blind randomized controlled trial) on 260 patients [258].

Ranitidine vs. Famotidine

Famotidine is available in 20 and 40 mg tablets and is approximately 7.5 times more potent than ranitidine [10, 259].

In a trial on 9 patients with Zollinger-Ellison syndrome, 0.24 g famotidine/day was as efficient at reducing the symptoms as 2.1 g ranitidine/day, and its effects lasted 30% longer [257].

However, famotidine (40 mg/day) was less effective in treating stomach ulcers than ranitidine (150 mg twice per day) in one study (double-blind randomized controlled trial) on 69 patients [260].

Both these drugs showed similar effectiveness against acid aspiration in a study (double-blind randomized controlled trial) on 50 patients undergoing surgery [261].

Ranitidine vs. Nizatidine

Nizatidine is as potent as ranitidine and is available as 150 and 300 mg capsules [10].

In a trial (double-blind randomized controlled trial) on 10 elderly patients, repeated intake of nizatidine caused lower accumulation of the drug in blood than the same treatment with ranitidine. Nizatidine was thus concluded to be safer for the repeated treatment of elderly patients [262].

Ranitidine 150 mg was as effective as nizatidine 150 mg at relieving the heartburn and acid regurgitation symptoms in 2 trials (double-blind randomized controlled trial) on 441 patients with gastroesophageal reflux in total [263].

Genetics Related to Ranitidine


OCT1 is responsible for transporting ranitidine into the liver for its subsequent degradation. Alleles with poor or absent ranitidine uptake capacity may reduce the breakdown of this drug [264].


FMO3 and the cytochromes CYP2C19, CYP1A2, and CYP2D6 degrade ranitidine in the liver before its elimination in urine [265].

SNPs associated with lower abundance of FMO3 (rs2064074, rs28363536, rs2266782, rs909530, rs2266780, and rs909531) may reduce ranitidine breakdown [266].


The CYP2C19 variant CYP2C19*17 (rs12248560) is associated with increased abundance of this enzyme and may enhance ranitidine breakdown [267].


CYP1A2 alleles may be less efficient at breaking down ranitidine based on their reduced activity on other drugs. In turn, the CYP1A2*1F variant caused increased activity of this enzyme [268, 269, 270, 271].


CYP2D6 alleles classified as having reduced or null activity may be less efficient at breaking down ranitidine [272].

If You Have Food Sensitivities

I recommend following my lectin avoidance diet, named as such because I think that lectins are the single major trigger of autoimmune disease. However, they are not the only trigger. And this diet is not a one-size-fits-all regimen. It may not suit EVERYONE’s needs, but it’s a good template from which to build a personalized diet.

If you suffer from food sensitivities, the Lectin Avoidance Diet helps you figure out which foods are inflammatory, and which are less inflammatory for you.

About the Author

Carlos Tello, PhD (Molecular Biology)

PhD (Molecular Biology)

Carlos received his PhD and MS from the Universidad de Sevilla.

Carlos spent 9 years in the laboratory investigating mineral transport in plants. He then started working as a freelancer, mainly in science writing, editing, and consulting. Carlos is passionate about learning the mechanisms behind biological processes and communicating science to both academic and non-academic audiences. He strongly believes that scientific literacy is crucial to maintain a healthy lifestyle and avoid falling for scams.

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